Alan Bryce, MD: I'm going to shift gears a little bit, let's talk about NMCRPC, nonmetastatic castration- resistant prostate cancer. This is a disease entity that has grown in prominence in the last few years, when we saw several clinical trials come out. In the era of advanced imaging, there becomes this whole conversation around, what is an NMCRPC, exactly? Dr Posadas, what are the treatment goals for patients with NMCRPC?

Edwin Posadas, MD: That's a great question, Alan. When we deal with men without obvious metastasis, one of our biggest goals is to stop them from developing metastatic disease, which is associated with morbidity and mortality. It was nice to have a new endpoint in trials of metastasis-free survival; it's clinically meaningful that the FDA accepted that. For those of us that have been doing prostate cancer trials, CRPC, and survival for the nonmetastatic patients, we must be able to show efficacy earlier, so that was a big deal. Dr Heath and Dr Zhang put it very nicely, with the fact that with the addition of PET scanning, the nonmetastatic space, it's sort of shrinking. I must be careful based on what my colleagues have already said, because the data that we have in the nonmetastatic space from trials of drugs like darolutamide, enzalutamide, and apalutamide, were done on the basis of conventional imaging and were shown to be a benefit to patients. You don't want to under serve, but you also don't want to over treat them at the same time. We don't know enough about the natural history of PSMA–positive-only disease at this point. I think as a field, we're taking on that challenge, but preserving quality of life and extending life are terribly important in the nonmetastatic setting for men who are very healthy. So that's a very important challenge for us in the field.

Alan Bryce, MD: How should the clinician listening to this be incorporating PSA doubling time? It's a concept that has only been partially applied in this space, but why do we care about PSA doubling time?

Edwin Posadas, MD: Alan, that's a wonderful and important point. As a field, we've recognized that PSA kinetics speak to the risk of metastasis. In the trials that we've done to evaluate therapies in the NMCRPC space, we've biased the patient populations to those who are higher risk, and these shorter PSA doubling times under 10 months. When you start to look at the raw trial data, you see that the PSA doubling times are pretty fast. This endpoint of delaying metastasis becomes meaningful in those populations, but it's a relatively simple calculation to make. You can do it off the cuff by looking at just a handful, but it's tricky. Not many clinicians are looking at the whole PSA history.Those of us on this call probably do because we're off writing trials to think about a triage patient, but for the busy clinician, it's a little more onerous. It is an important thing that should be considered in treating men with both metastatic–castration-sensitive and castration-resistant prostate cancer.

Transcript edited for clarity.